Author: Sarah Shim
Submitted: December 5, 2009
Word Count: 3025
Title: Lack of Influence of Consumed 2-Phenylethylamine in Chocolate Cravings and Addiction
Abstract:
From the time of the ancient Maya and Aztec to present day, chocolate has been a food highly desired and enjoyed. This “gift of the gods” that was once only offered to the highest and richest of society can now be obtained and enjoyed by people of all ages and locations. In most recent times, the topic of chocolate cravings and addiction has sparked the interest of scientists and those who are not scientists alike. Whether or not chocolate is addictive and if so, the cause of the addiction is still under much debate. This paper is a compilation of the evidence that has been collected regarding the role of 2-phenylethylamine (2-PEA), one of the biologically active components of chocolate commonly suggested to make chocolate addictive. It has been concluded that this particular biogenic amine by itself does not cause chocolate cravings or addictions. In vivo, the metabolism of consumed 2-PEA is catalyzed by monoamine oxidase B in the brain, eliminating nearly all of the amine very rapidly. In addition, foods that have much higher levels of 2-PEA are not craved as is chocolate. Therefore, the theory that chocolate cravings are made because of a deficiency of the amine in the body is not valid. Lastly, the 2-PEA in chocolate is too low to have lasting effects on the brain, and therefore, could not by itself cause chocolate addiction.
Introduction:
Is chocolate a food, or is it a drug? Though this simple question about a seemingly harmless substance may seem frivolous and nonsensical to some, the issue raised has been the topic of much research in recent years. Part of the reason for the scientific interest in chocolate has been due to the fact that chocolate is, by far, the most craved food among North Americans and comprises 49% of all food cravings (1). Chocolate is made from the cocoa beans of the cacao tree. These trees, which were once localized to equatorial parts of the Americas, are now being cultivated in tropical regions all over the world (10), keeping up with people’s need to satiate their hunger for chocolate. Carl Linnaeus, founder of modern taxonomy, fittingly named this beloved tree Theobroma cacao, theobroma which signifies “food of the gods” (10). What was once only served to the elite is now available to the public in various forms and sizes and is, for the most part, enjoyed. On the other hand, the supposed addictiveness of chocolate has been analyzed in great detail and continues to be the topic of many research projects. However, even amongst those who assert that chocolate is addictive, there is much controversy over the cause of the addiction.
During recent years, many scientists have acknowledged that chocolate is, in fact, addictive to those who are susceptible. Whereas chocolate cravings can be defined as the strong but ephemeral desire to obtain and consume chocolate, addiction is a far more complicated concept. Conventionally, addiction, whether of chocolate or drugs, is defined as “a compulsion to use a substance that results in excessive and uncontrolled consumption and existence of withdrawal symptoms when the substance is withheld” (1). Among the researchers who agree in chocolate addiction, most categorize the cause for the chocolate addiction into the following four main categories: chocolate’s sensory characteristics (such as taste, aroma, and texture), hedonistic characteristics (partly from the high fat and sugar content), method of self-medication for nutritional deficiencies in the body, and biologically active components in that are naturally found in chocolate (1).
The biologically active components found in chocolate include alkaloid methylxanthines of which theobromine and caffeine are the most prominent, unsaturated N-acylethanolamines, and biogenic amines. One particular group of biologically active components of chocolate is biogenic amines (2). In one study of the determination of the biogenic amines in chocolate through high-performance liquid chromatography (HPLC), four major amines were found to be present in several kinds of chocolate and chocolate liquors, with tyramine and phenylethylamine (PEA) being the most notable (2). In addition to HPLC, thin-layer chromatography has also been used during the study to show the presence of the four biogenic amines in chocolate (2). Moreover, PEA has been identified in chocolate through mass spectrometry as well (8). Since the more than three hundred compounds present in chocolate (3) cannot all be analyzed, PEA and its role – or lack thereof – in chocolate addiction will be the focus of this paper.
Background on Phenylethylamine:
The endogenous amine phenylethylamine (PEA) is the decarboxylated form of the ubiquitous amino acid phenylalanine (14). The specific PEA present in chocolate is 2-phenylethylamine, which is more commonly used than its systematic name N-ethylaniline. 2-PEA is a trace endogenous amine that has been identified in the several mammalian tissues (15). Studies of the presence and distribution of 2-PEA in rats have shown that this biogenic amine is present in the brain, heart, kidney, liver, lung, and spleen (9). When dealing with chocolate and the function of the 2-PEA in it, the organ of special interest is the brain. As an endogenous component of the human brain, 2-PEA takes a part in cerebral transmission (6). This biogenic amine has the ability to cross the presynaptic membrane of brain cells and increases the effectiveness of the postsynaptic effects of dopamine, a neurotransmitter involved in the feeling of pleasure and reward (7). In addition to enhancing the effects of dopamine, according to one study on the role of 2-PEA in nigrostriatal dopamine neurotransmission, 2-PEA also stimulates the release of dopamine and even behaves as a receptor to dopamine although only for a very brief and rapid encounter (7). Along with aiding in dopamine neurotransmission, some researchers suspect that 2-PEA may also act as a neuromodulator during catecholamine neurotransmission in the brain (7).
Furthermore, studies have been done to show that PEA can change a person’s mood (3, 5). This amine has been proposed to have the ability to lessen the effect of depression in certain people and to create a feeling of euphoria in others (3). Recently, it has been reported that PEA stimulates the portion of the brain called the hypothalamus (5). By doing so, PEA is thought to induce the feeling of euphoria and, at the same time, to affect the levels of the neurotransmitters 5-hydroxytrytamine (also known as serotonin) and endorphins in the brain (5). These actions would, therefore, enhance the mood lifting of person (5). As a result, a deficiency of this biogenic amine in the brain can lead to, in some cases, the development of depression (3). Unsurprisingly, the characteristics of endogenous 2-PEA mentioned above have led some researchers to speculate that 2-PEA may be the cause of chocolate addiction. However, the two factors of 2-PEA in chocolate have led this researcher to conclude otherwise. First of all, any 2-PEA that is consumed, such as when chocolate is eaten, is quickly metabolized upon entry into the body (1). Secondly, the concentration of 2-PEA in chocolate is too low to have a profound effect (1). Thus, in the next two sections of this paper, these two factors and what it means for 2-PEA as the cause of chocolate cravings and addiction will be considered and analyzed.
Rapid Metabolism of Consumed 2-PEA:
One of the arguments some researchers make is that since 2-PEA is so structurally similar amphetamine, when 2-PEA is in a food like chocolate and that food is consumed in large amounts, the amine can have the same effect as amphetamine (3). Like the well known drug cocaine, amphetamine is also a drug often used as a brain stimulant due to its ability to cause intense psychomotor activation, decreased fatigue, and a feeling of happiness (3, 22). In addition, this drug can produce long-lasting behavioral effects such as addiction to the substance (22). Structurally, 2-PEA is very similar to amphetamine, with the only structural difference being the lack of the alpha methyl group in the alkyl side chain of 2-PEA (15). Moreover, 2-PEA, like amphetamine, is a brain stimulant (3). One study performed by Borison et al. of 2-PEA in rats have provided experimental evidence that in addition to structural similarities, endogenous 2-PEA has pharmacological similarities with amphetamine as well (23). Therefore, the argument that endogenous 2-PEA could take part in mediating the central actions of amphetamine has also been made (23).
However, unlike the 2-PEA that is naturally present in the brain, 2-PEA that is consumed has lower potency than amphetamine due to its rapid metabolism in vivo (15). The metabolism of 2-PEA involves its ultimate conversion to phenylacetic acid. However, before it is changed to the acid, 2-PEA is first converted to phenylacetaldehyde (6). Studies have shown that this latter conversion requires catalysis by the enzyme monoamine oxidase B (6, 20). In one study performed by Panoutsopoulos et al., 2-PEA (at 2 x 10^-3 M) was treated with 17.25 mg of monoamine oxidase (6). Within the first sixty minutes, phenylacetaldehyde (at 0.66 x 10^-3 M) was produced. Furthermore, as a greater amount of the oxidase was used (40.25 mg), an increase in the production of phenylacetaldehyde (at 1.17 x 10^-3 M) was observed. In these experiments, 50 – 100% of the PEA was converted into its aldehyde form within two hours (6). Once the 2-PEA is converted into phenylacetaldehyde, this intermediate is further converted into the phenylacetic acid with the aid of aldehyde dehydrogenase, which is the prominent enzyme involved with this second oxidation of 2-PEA (6).
While the experiment performed tested the metabolism of 2-PEA in vitro, in vivo, the metabolism of consumed 2-PEA occurs at an extremely rapid rate (15). One comparative study of 2-PEA with amphetamine performed by Karoum et al. showed that once administered, both 2-PEA and amphetamine rapidly enter the brain. However, though quick to enter, amphetamine is eliminated slowly (16). In another study, Durden and Philips analyzed the turnover rates of 2-PEA in vivo in the rat brain though kinetic measurements (17). Durden and Philips found that 2-PEA is oxidized very rapidly in the brain. Moreover, compared with that of other typical neurotransmitters, the half-life of the 2-PEA was much shorter (17). Likewise, the study of Karoum et al. also showed that 2-PEA is quick to enter the brain, and furthermore, that it is nearly completely eliminated (i.e. oxidized) within 30 minutes of administration of the amine (16).
In the study performed by Karoum et al., 20 mg of 2-PEA was administered per 1 kg of the rat (16). Immediately after the administration, clear behavioral changes such as salivation, tremor, and occasional squeaking were observed in the rats. However, these sudden effects only lasted from a brief period of time (about 5 – 20 minutes) with the greatest response at about 10 minutes. The highest concentration of 2-PEA in the brain was observed 15 minutes after the administration. This sudden increase in the biogenic amine caused an increase in the concentration of endogenous PEA in the hypothalamus. Nevertheless, after this brief period, the concentration of endogenous PEA began to decrease. As a matter of fact, the PEA concentration actually went down to a level considerably lower than normal (16).
In the brain, monoamine oxidase B keeps 2-PEA from building up through its breakdown catabolism (18). As mentioned above, monoamine oxidase B oxidatively deaminates 2-PEA, which studies have shown to be one of the specific substrates for monoamine oxidase B (20). One study performed by Lewinsohn et al. of the distribution of this enzyme in humans and rats have shown that the brain as well as the liver show the highest levels of monoamine oxidase B activity (21). Also in this study, it is shown that 2-PEA is only oxidized by monoamine oxidase B (21). If the 2-PEA that was consumed were to cause a long-lasting effect such as addiction, the amine would have to be eliminated slowly in the brain, such as is the case with amphetamine. However, the brain contains high levels of the enzyme needed for the rapid oxidation of 2-PEA. As was shown in the study performed by Panoutsopoulos et al., the more oxidase is present, the more 2-PEA is oxidized into its aldehyde form. Therefore, the rapid metabolism of consumed 2-PEA in vivo supports that any consumed 2-PEA does not make the consumed food addicting.
Low Concentration of 2-PEA in Chocolate:
Another popular notion is that the body causes chocolate cravings as a means of self-medication for low levels of PEA in the brain. Logically, if cravings are the results of nutritional deficiencies – which, in this case, would be 2-PEA – in the body, foods with high levels of 2-PEA should be craved. Yet other foods that contain a significant greater amount of this biogenic amine are not craved as chocolate often is. For instance, the level of 2-PEA is much higher in fermented sausages, certain types of mushrooms, and cheeses (12). In one study of the presence of PEA in mushrooms, the PEA content in the mushroom species Psilocybe semilanceata was found to be as high as 146 ug per gram of mushroom (14). In a different study of the occurrence of biologically active amines in food by ten Brink et al., Dutch cheese was found to have approximately 9 mg of PEA per kilogram of cheese, while the highest level was 46 mg per kilogram (19). In the same study, fermented cheese was found to have an average of 14 mg of PEA per kilogram of sausage, reaching as high as 45 mg per kilogram (19).
Compared to the foods mentioned above, chocolate has an extremely low concentration of PEA. Although 2-PEA is also found in the cacao beans, according to one study of the thermal processing of cacao performed by Granvogl et al., the process of the fermentation of these beans, which is the initial step taken during the production of chocolate, is suggested to cause an increase in the concentration of many of the amines present in the cacao beans, including 2-PEA (4, 1). In addition, Granvogl et al. found that upon roasting the beans, one of the subsequent steps in chocolate production after fermentation, there is an even more significant formation of the amines (4). Therefore, compared with the original cacao beans, the chocolate product has more amines such as the 2-PEA.
Nevertheless, despite the increases in the amount of amines present in chocolate due to the production process, the level of 2-PEA is still quite low. In a review of the levels of biogenic amines present in foods, the average 2-PEA content in milk chocolate was reported as about 0.4 – 6.6 ug per gram of chocolate (13). Even though a 2-PEA level of 0.4 – 6.6 ug per gram is high compared to most other foods, it is far less than the amount in cheeses, some mushrooms, and fermented sausage, which contain a significantly greater amount of 2-PEA (12, 14, 19). Thus, the chocolate cravings were the result of the body’s efforts to self-medicate a deficiency of 2-PEA, these foods with the higher level of 2-PEA should be craved. However, whereas chocolate, which contains a minimal amount of 2-PEA, is one of the top craved foods, the 2-PEA-rich cheese, sausage, and mushrooms are not among the commonly craved foods (1).
In addition, many researchers recognize that the biologically active ingredients such as 2-PEA, theobromine, tyramine, caffeine, and many others in chocolate have the potential to be psychoactive agents. However, at the same time, the same researchers assert that even if these components had the ability to and actually did act as psychoactive agents once consumed, they are at levels far too low in chocolate to have any noticeable or lasting effect on the central nervous system of the chocolate consumer (11). Therefore, the theory of chocolate cravings as a form of self-medication for the lack of 2-PEA in the body is not supported by the findings of this paper.
Conclusions:
The question of whether or not chocolate truly is addictive or not still has not been answered yet. In addition, even if these chocolate addictions were true, the underlying cause of the addictions is still unknown. However, the evidence collected for this paper has led to the conclusion that at least 2-PEA by itself is not the cause of the alleged chocolate addictions. First of all, once the chocolate is consumed, the 2-PEA present in the chocolate is quickly metabolized through the aid of monoamine oxidase B, which catalyzes the oxidation of 2-PEA to phenylacetaldehyde and prevents PEA from accumulating in the brain (6, 16, 18). The relative amounts of 2-PEA used during the experiments, such as the one performed by Karoum et al. (16), are significantly greater than the amount of 2-PEA present in chocolate.
For instance, the 20 mg of 2-PEA per kilogram of rat administered during the study by Karoum et al. was almost completely eliminated within 30 minutes. Furthermore, in the end, the 2-PEA administered did not increase the level of endogenous PEA but actually caused the level to decrease below the original level (16). A regular Hershey’s milk chocolate bar is 43 grams (24). Therefore, since there is an average of 0.4 – 6.6 ug of 2-PEA per gram of chocolate (13), about 0.0172 – 0.284 mg of 2-PEA is contained in the entire chocolate bar. Therefore, if a person of 60 kg were to consume the entire Hershey’s chocolate bar, the amount of 2-PEA eaten would be 0.287 – 4.73 ug per kilogram. This is far less 2-PEA than the 20 mg/kg that was administered to the rat. Therefore, since the 2-PEA was completely metabolized in 30 minutes in the rat, even less time should be needed to metabolize the 2-PEA consumed by a human.
Moreover, the common claim that the body may self-mediate for 2-PEA deficiencies through causing chocolate cravings is not supported. Foods with significantly higher levels of 2-PEA than chocolate are not craved as much if at all. Lastly, the level of 2-PEA in chocolate is too low to have an effect on the brain and thereby cause addiction to chocolate Thus, due to the factors mentioned above and the evidence found, it is concluded that by itself, 2-PEA does not cause chocolate cravings or addiction.
References:
(1) Bruinsma, K.; Taren, D. L. J. Am. Diet. Assoc. 1999, 99, 1249-1256. source
(2) Hurst, W. J.; Toomey, P. B. Analyst1981, 106, 394-402. source
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(4) Granvogl, M.; Bugan, S.; Schieberle, P. J Agric Food Chem2006, 54, 1730-1739. source
(5) Afoakwa, E. South African Journal of Clinical Nutrition2008, 21. source
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(7) Barroso, N.; Rodriguez, M. Eur. J. Pharmacol. 1996, 297, 195-203. source
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(11) Parker, G.; Parker, I.; Brotchie, H. J. Affect. Disord. 2006, 92, 149-159. source
(12) Santos, M. H. S. Int. J. Food Microbiol. 1996, 29, 213-231. source
(13) Hurst, W. J.; Martin, R. A. J.; Zoumas, B. L. Nutrition Reports International1982, 26, 1081-1086. source
(14) Beck, O.; Helander, A.; Karlson-Stiber, C.; Stephansson, N. J. Anal. Toxicol. 1998, 22, 45-49(5). source
(15) Gilbert, D.; Cooper, S. J. Eur. J. Pharmacol. 1983, 95, 311-314. source
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(17) Burden, D. A.; Philips, S. R. J. Neurochem. 1980, 34, 1725-1732. source
(18) Ghozlan, A.; Varoquaux, O.; Abadie, V. Mol. Genet. Metab. 2004, 83, 337-340. source
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(20) Yang, H. -. T.; Neff, N. H. Journal of Pharmacology and Experimental Therapeutics1973, 187, 365-371. source
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(24) Hershey's Chocolate Bar. source
Sarah Shim Log
Author: Sarah ShimSubmitted: December 5, 2009
Word Count: 3025
Title: Lack of Influence of Consumed 2-Phenylethylamine in Chocolate Cravings and Addiction
Abstract:
From the time of the ancient Maya and Aztec to present day, chocolate has been a food highly desired and enjoyed. This “gift of the gods” that was once only offered to the highest and richest of society can now be obtained and enjoyed by people of all ages and locations. In most recent times, the topic of chocolate cravings and addiction has sparked the interest of scientists and those who are not scientists alike. Whether or not chocolate is addictive and if so, the cause of the addiction is still under much debate. This paper is a compilation of the evidence that has been collected regarding the role of 2-phenylethylamine (2-PEA), one of the biologically active components of chocolate commonly suggested to make chocolate addictive. It has been concluded that this particular biogenic amine by itself does not cause chocolate cravings or addictions. In vivo, the metabolism of consumed 2-PEA is catalyzed by monoamine oxidase B in the brain, eliminating nearly all of the amine very rapidly. In addition, foods that have much higher levels of 2-PEA are not craved as is chocolate. Therefore, the theory that chocolate cravings are made because of a deficiency of the amine in the body is not valid. Lastly, the 2-PEA in chocolate is too low to have lasting effects on the brain, and therefore, could not by itself cause chocolate addiction.
Introduction:
Is chocolate a food, or is it a drug? Though this simple question about a seemingly harmless substance may seem frivolous and nonsensical to some, the issue raised has been the topic of much research in recent years. Part of the reason for the scientific interest in chocolate has been due to the fact that chocolate is, by far, the most craved food among North Americans and comprises 49% of all food cravings (1). Chocolate is made from the cocoa beans of the cacao tree. These trees, which were once localized to equatorial parts of the Americas, are now being cultivated in tropical regions all over the world (10), keeping up with people’s need to satiate their hunger for chocolate. Carl Linnaeus, founder of modern taxonomy, fittingly named this beloved tree Theobroma cacao, theobroma which signifies “food of the gods” (10). What was once only served to the elite is now available to the public in various forms and sizes and is, for the most part, enjoyed. On the other hand, the supposed addictiveness of chocolate has been analyzed in great detail and continues to be the topic of many research projects. However, even amongst those who assert that chocolate is addictive, there is much controversy over the cause of the addiction.
During recent years, many scientists have acknowledged that chocolate is, in fact, addictive to those who are susceptible. Whereas chocolate cravings can be defined as the strong but ephemeral desire to obtain and consume chocolate, addiction is a far more complicated concept. Conventionally, addiction, whether of chocolate or drugs, is defined as “a compulsion to use a substance that results in excessive and uncontrolled consumption and existence of withdrawal symptoms when the substance is withheld” (1). Among the researchers who agree in chocolate addiction, most categorize the cause for the chocolate addiction into the following four main categories: chocolate’s sensory characteristics (such as taste, aroma, and texture), hedonistic characteristics (partly from the high fat and sugar content), method of self-medication for nutritional deficiencies in the body, and biologically active components in that are naturally found in chocolate (1).
The biologically active components found in chocolate include alkaloid methylxanthines of which theobromine and caffeine are the most prominent, unsaturated N-acylethanolamines, and biogenic amines. One particular group of biologically active components of chocolate is biogenic amines (2). In one study of the determination of the biogenic amines in chocolate through high-performance liquid chromatography (HPLC), four major amines were found to be present in several kinds of chocolate and chocolate liquors, with tyramine and phenylethylamine (PEA) being the most notable (2). In addition to HPLC, thin-layer chromatography has also been used during the study to show the presence of the four biogenic amines in chocolate (2). Moreover, PEA has been identified in chocolate through mass spectrometry as well (8). Since the more than three hundred compounds present in chocolate (3) cannot all be analyzed, PEA and its role – or lack thereof – in chocolate addiction will be the focus of this paper.
Background on Phenylethylamine:
The endogenous amine phenylethylamine (PEA) is the decarboxylated form of the ubiquitous amino acid phenylalanine (14). The specific PEA present in chocolate is 2-phenylethylamine, which is more commonly used than its systematic name N-ethylaniline. 2-PEA is a trace endogenous amine that has been identified in the several mammalian tissues (15). Studies of the presence and distribution of 2-PEA in rats have shown that this biogenic amine is present in the brain, heart, kidney, liver, lung, and spleen (9). When dealing with chocolate and the function of the 2-PEA in it, the organ of special interest is the brain. As an endogenous component of the human brain, 2-PEA takes a part in cerebral transmission (6). This biogenic amine has the ability to cross the presynaptic membrane of brain cells and increases the effectiveness of the postsynaptic effects of dopamine, a neurotransmitter involved in the feeling of pleasure and reward (7). In addition to enhancing the effects of dopamine, according to one study on the role of 2-PEA in nigrostriatal dopamine neurotransmission, 2-PEA also stimulates the release of dopamine and even behaves as a receptor to dopamine although only for a very brief and rapid encounter (7). Along with aiding in dopamine neurotransmission, some researchers suspect that 2-PEA may also act as a neuromodulator during catecholamine neurotransmission in the brain (7).
Furthermore, studies have been done to show that PEA can change a person’s mood (3, 5). This amine has been proposed to have the ability to lessen the effect of depression in certain people and to create a feeling of euphoria in others (3). Recently, it has been reported that PEA stimulates the portion of the brain called the hypothalamus (5). By doing so, PEA is thought to induce the feeling of euphoria and, at the same time, to affect the levels of the neurotransmitters 5-hydroxytrytamine (also known as serotonin) and endorphins in the brain (5). These actions would, therefore, enhance the mood lifting of person (5). As a result, a deficiency of this biogenic amine in the brain can lead to, in some cases, the development of depression (3). Unsurprisingly, the characteristics of endogenous 2-PEA mentioned above have led some researchers to speculate that 2-PEA may be the cause of chocolate addiction. However, the two factors of 2-PEA in chocolate have led this researcher to conclude otherwise. First of all, any 2-PEA that is consumed, such as when chocolate is eaten, is quickly metabolized upon entry into the body (1). Secondly, the concentration of 2-PEA in chocolate is too low to have a profound effect (1). Thus, in the next two sections of this paper, these two factors and what it means for 2-PEA as the cause of chocolate cravings and addiction will be considered and analyzed.
Rapid Metabolism of Consumed 2-PEA:
One of the arguments some researchers make is that since 2-PEA is so structurally similar amphetamine, when 2-PEA is in a food like chocolate and that food is consumed in large amounts, the amine can have the same effect as amphetamine (3). Like the well known drug cocaine, amphetamine is also a drug often used as a brain stimulant due to its ability to cause intense psychomotor activation, decreased fatigue, and a feeling of happiness (3, 22). In addition, this drug can produce long-lasting behavioral effects such as addiction to the substance (22). Structurally, 2-PEA is very similar to amphetamine, with the only structural difference being the lack of the alpha methyl group in the alkyl side chain of 2-PEA (15). Moreover, 2-PEA, like amphetamine, is a brain stimulant (3). One study performed by Borison et al. of 2-PEA in rats have provided experimental evidence that in addition to structural similarities, endogenous 2-PEA has pharmacological similarities with amphetamine as well (23). Therefore, the argument that endogenous 2-PEA could take part in mediating the central actions of amphetamine has also been made (23).
However, unlike the 2-PEA that is naturally present in the brain, 2-PEA that is consumed has lower potency than amphetamine due to its rapid metabolism in vivo (15). The metabolism of 2-PEA involves its ultimate conversion to phenylacetic acid. However, before it is changed to the acid, 2-PEA is first converted to phenylacetaldehyde (6). Studies have shown that this latter conversion requires catalysis by the enzyme monoamine oxidase B (6, 20). In one study performed by Panoutsopoulos et al., 2-PEA (at 2 x 10^-3 M) was treated with 17.25 mg of monoamine oxidase (6). Within the first sixty minutes, phenylacetaldehyde (at 0.66 x 10^-3 M) was produced. Furthermore, as a greater amount of the oxidase was used (40.25 mg), an increase in the production of phenylacetaldehyde (at 1.17 x 10^-3 M) was observed. In these experiments, 50 – 100% of the PEA was converted into its aldehyde form within two hours (6). Once the 2-PEA is converted into phenylacetaldehyde, this intermediate is further converted into the phenylacetic acid with the aid of aldehyde dehydrogenase, which is the prominent enzyme involved with this second oxidation of 2-PEA (6).
While the experiment performed tested the metabolism of 2-PEA in vitro, in vivo, the metabolism of consumed 2-PEA occurs at an extremely rapid rate (15). One comparative study of 2-PEA with amphetamine performed by Karoum et al. showed that once administered, both 2-PEA and amphetamine rapidly enter the brain. However, though quick to enter, amphetamine is eliminated slowly (16). In another study, Durden and Philips analyzed the turnover rates of 2-PEA in vivo in the rat brain though kinetic measurements (17). Durden and Philips found that 2-PEA is oxidized very rapidly in the brain. Moreover, compared with that of other typical neurotransmitters, the half-life of the 2-PEA was much shorter (17). Likewise, the study of Karoum et al. also showed that 2-PEA is quick to enter the brain, and furthermore, that it is nearly completely eliminated (i.e. oxidized) within 30 minutes of administration of the amine (16).
In the study performed by Karoum et al., 20 mg of 2-PEA was administered per 1 kg of the rat (16). Immediately after the administration, clear behavioral changes such as salivation, tremor, and occasional squeaking were observed in the rats. However, these sudden effects only lasted from a brief period of time (about 5 – 20 minutes) with the greatest response at about 10 minutes. The highest concentration of 2-PEA in the brain was observed 15 minutes after the administration. This sudden increase in the biogenic amine caused an increase in the concentration of endogenous PEA in the hypothalamus. Nevertheless, after this brief period, the concentration of endogenous PEA began to decrease. As a matter of fact, the PEA concentration actually went down to a level considerably lower than normal (16).
In the brain, monoamine oxidase B keeps 2-PEA from building up through its breakdown catabolism (18). As mentioned above, monoamine oxidase B oxidatively deaminates 2-PEA, which studies have shown to be one of the specific substrates for monoamine oxidase B (20). One study performed by Lewinsohn et al. of the distribution of this enzyme in humans and rats have shown that the brain as well as the liver show the highest levels of monoamine oxidase B activity (21). Also in this study, it is shown that 2-PEA is only oxidized by monoamine oxidase B (21). If the 2-PEA that was consumed were to cause a long-lasting effect such as addiction, the amine would have to be eliminated slowly in the brain, such as is the case with amphetamine. However, the brain contains high levels of the enzyme needed for the rapid oxidation of 2-PEA. As was shown in the study performed by Panoutsopoulos et al., the more oxidase is present, the more 2-PEA is oxidized into its aldehyde form. Therefore, the rapid metabolism of consumed 2-PEA in vivo supports that any consumed 2-PEA does not make the consumed food addicting.
Low Concentration of 2-PEA in Chocolate:
Another popular notion is that the body causes chocolate cravings as a means of self-medication for low levels of PEA in the brain. Logically, if cravings are the results of nutritional deficiencies – which, in this case, would be 2-PEA – in the body, foods with high levels of 2-PEA should be craved. Yet other foods that contain a significant greater amount of this biogenic amine are not craved as chocolate often is. For instance, the level of 2-PEA is much higher in fermented sausages, certain types of mushrooms, and cheeses (12). In one study of the presence of PEA in mushrooms, the PEA content in the mushroom species Psilocybe semilanceata was found to be as high as 146 ug per gram of mushroom (14). In a different study of the occurrence of biologically active amines in food by ten Brink et al., Dutch cheese was found to have approximately 9 mg of PEA per kilogram of cheese, while the highest level was 46 mg per kilogram (19). In the same study, fermented cheese was found to have an average of 14 mg of PEA per kilogram of sausage, reaching as high as 45 mg per kilogram (19).
Compared to the foods mentioned above, chocolate has an extremely low concentration of PEA. Although 2-PEA is also found in the cacao beans, according to one study of the thermal processing of cacao performed by Granvogl et al., the process of the fermentation of these beans, which is the initial step taken during the production of chocolate, is suggested to cause an increase in the concentration of many of the amines present in the cacao beans, including 2-PEA (4, 1). In addition, Granvogl et al. found that upon roasting the beans, one of the subsequent steps in chocolate production after fermentation, there is an even more significant formation of the amines (4). Therefore, compared with the original cacao beans, the chocolate product has more amines such as the 2-PEA.
Nevertheless, despite the increases in the amount of amines present in chocolate due to the production process, the level of 2-PEA is still quite low. In a review of the levels of biogenic amines present in foods, the average 2-PEA content in milk chocolate was reported as about 0.4 – 6.6 ug per gram of chocolate (13). Even though a 2-PEA level of 0.4 – 6.6 ug per gram is high compared to most other foods, it is far less than the amount in cheeses, some mushrooms, and fermented sausage, which contain a significantly greater amount of 2-PEA (12, 14, 19). Thus, the chocolate cravings were the result of the body’s efforts to self-medicate a deficiency of 2-PEA, these foods with the higher level of 2-PEA should be craved. However, whereas chocolate, which contains a minimal amount of 2-PEA, is one of the top craved foods, the 2-PEA-rich cheese, sausage, and mushrooms are not among the commonly craved foods (1).
In addition, many researchers recognize that the biologically active ingredients such as 2-PEA, theobromine, tyramine, caffeine, and many others in chocolate have the potential to be psychoactive agents. However, at the same time, the same researchers assert that even if these components had the ability to and actually did act as psychoactive agents once consumed, they are at levels far too low in chocolate to have any noticeable or lasting effect on the central nervous system of the chocolate consumer (11). Therefore, the theory of chocolate cravings as a form of self-medication for the lack of 2-PEA in the body is not supported by the findings of this paper.
Conclusions:
The question of whether or not chocolate truly is addictive or not still has not been answered yet. In addition, even if these chocolate addictions were true, the underlying cause of the addictions is still unknown. However, the evidence collected for this paper has led to the conclusion that at least 2-PEA by itself is not the cause of the alleged chocolate addictions. First of all, once the chocolate is consumed, the 2-PEA present in the chocolate is quickly metabolized through the aid of monoamine oxidase B, which catalyzes the oxidation of 2-PEA to phenylacetaldehyde and prevents PEA from accumulating in the brain (6, 16, 18). The relative amounts of 2-PEA used during the experiments, such as the one performed by Karoum et al. (16), are significantly greater than the amount of 2-PEA present in chocolate.
For instance, the 20 mg of 2-PEA per kilogram of rat administered during the study by Karoum et al. was almost completely eliminated within 30 minutes. Furthermore, in the end, the 2-PEA administered did not increase the level of endogenous PEA but actually caused the level to decrease below the original level (16). A regular Hershey’s milk chocolate bar is 43 grams (24). Therefore, since there is an average of 0.4 – 6.6 ug of 2-PEA per gram of chocolate (13), about 0.0172 – 0.284 mg of 2-PEA is contained in the entire chocolate bar. Therefore, if a person of 60 kg were to consume the entire Hershey’s chocolate bar, the amount of 2-PEA eaten would be 0.287 – 4.73 ug per kilogram. This is far less 2-PEA than the 20 mg/kg that was administered to the rat. Therefore, since the 2-PEA was completely metabolized in 30 minutes in the rat, even less time should be needed to metabolize the 2-PEA consumed by a human.
Moreover, the common claim that the body may self-mediate for 2-PEA deficiencies through causing chocolate cravings is not supported. Foods with significantly higher levels of 2-PEA than chocolate are not craved as much if at all. Lastly, the level of 2-PEA in chocolate is too low to have an effect on the brain and thereby cause addiction to chocolate Thus, due to the factors mentioned above and the evidence found, it is concluded that by itself, 2-PEA does not cause chocolate cravings or addiction.
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